An Additional Spirocyclization for Duocarmycin SA

A unique alternative to the p-spirocyclization for activation of compounds containing the duocarmycin SA alkylation subunit was established involving indole NH deprotonation and subsequent cyclopropane formation. The structural characterization of an alternative spirocyclization product and the establishment of its relative reactivity, intrinsic reaction regioselectivity, biological activity, and DNA alkylation properties (selectivity, rate, and efficiency) including the isolation, characterization, and quantitation of its adenine N3 adduct are disclosed.